The use of biological fluids for therapeutic human application such as plasmas, albumin, live vaccines, stem cells requires that they are absolutely devoid of bacterial contamination. It has been found that filtering, and possibly other traditional methods, may fail to eliminate all forms of organisms, leading to possible contamination or experimental artifacts.
It is believed that certain pathologies are associated with bacteria or bacterial forms which are difficult to detect, and which may pass through nano-porous barriers. This leads to possible errors in diagnosis or causation, and which may lead to erroneous treatment and impede prevention.
See, Hopert, Anne, Uphoff, Cord C., Wirth, Manfred, Hauser, Hansjorg, and Drexler, Hans G., “Specificity and sensitivity of Polymerase Chain Reaction (PCR) in comparison with other methods for the detection of mycoplasma contamination in cell lines”, J. Immunological Methods, 164(1993):91-100, expressly incorporated herein by reference.
Kajander, E. O., et al., “Comparison of Staphylococci and novel Bacteria-Like Particles from blood”, Zbl. Bakt. Suppl. 26, 1994, expressly incorporated herein by reference.
Akerman, Kari K., “Scanning Electron Microscopy of Nanobacteria—Novel Biofilm Producing Organisms in Blood”, Scanning Vol. 15, Suppl. III (1993), expressly incorporated herein by reference. www.newcastle.edu.au/discipline/biology/projects/hons_cpru.html, expressly incorporated herein by reference.
Cifticioglu, Neva, et al., “Apoptotic effect of nanobacteria on cultured mammalian cells”, Mol. Biol. Cell. Suppl., Vol. 7 (1996):517a
Cifticioglu, Neva, et al., “A new potential threat in antigen and antibody products: Nanobacteria”, Vaccines 97, Brown et al. Ed., Cold Spring Harbor Laboratory Press, New York, 1997, expressly incorporated herein by reference.
Baseman, Joel B., et al., “Mycoplasmas: Sophisticated, Reemerging, and Burdened by their Notoriety”, EID Vol. 3, No 1 www.cdc.gov/ncidod/EID/vol3no1/baseman.htm, expressly incorporated herein by reference.
Relman, David A., “Detection and Identification of Previously Unrecognized Microbial Pathogens”, EID Vol. 4, No 3 www.cdc.gov/ncidod/EID/vol4no3/relman.htm, expressly incorporated herein by reference.
Mattman, Lida H., Cell Wall Deficient Forms-Stealth Pathogens, 2nd Ed., CRC Press (1993), expressly incorporated herein by reference.
U.S. Pat. No. 5,688,646, expressly incorporated herein by reference, describes novel mycoplasmas which are prominent in patients who are thought to be suffering from AIDS. Devices are also provided for the in vitro detection of mycoplasmas in biological fluid by means of a reagent which is specific for the mycoplasma group without being specific for particular species within said group. Devices for testing mycoplasma sensitivity to antibiotics are also described.
See the following, each of which and cited references is expressly incorporated herein by reference in their entirety:
Pat. NoTitle6,562,611FEN-1 endonucleases, mixtures and cleavage methods6,558,902Infrared matrix-assisted laser desorption/ionization mass spectrometric analysis ofmacromolecules6,555,357FEN-1 endonuclease, mixtures and cleavage methods6,555,338NrdF from Staphylococcus aureus6,537,774UPS (undecaprenyl diphosphate synthase6,492,113Detection of Mycoplasma genus and species in patients with chronic fatigue syndromeand fibromyalgia6,489,139FabZ from Staphylococcus aureus6,489,110EF-Tu mRNA as a marker for viability of bacteria6,458,572Phosphatidylglycerophosphate synthase from Staphylococcus aureus6,458,535Detection of nucleic acids by multiple sequential invasive cleavages 026,448,037PgsA6,432,703RATC from Streptococcus pneumoniae6,410,286Asparaginyl tRNA synthetase from Staphylococcus Aureus6,399,343inFB6,372,424Rapid detection and identification of pathogens6,361,965YfiI pseudouridine synthase6,353,093gidB6,350,600trmD6,348,582Prokaryotic polynucleotides polypeptides and their uses6,348,328Compounds6,348,314Invasive cleavage of nucleic acids6,346,397GyrA6,340,564yhxB6,331,411TopA6,326,172ytgP6,312,932Yfil pseudouridine synthase6,309,8666-phosphogluconate dehydrogenase6,303,771Pth6,294,652Response regulator6,294,357FabF from Staphylococcus aureus6,287,807MurF6,287,804nrdG6,277,595FabZ6,274,719Gcp6,274,361pth6,270,762tdk6,268,177Isolated nucleic acid encoding nucleotide pyrophosphorylase6,261,802Ups (ugc)6,261,769Intergenic spacer target sequence for detecting and distinguishing Chlamydial speciesor strains6,255,075Bira6,251,631nadE from Streptococcus pneumoniae6,251,629ABC transporter6,248,721Method of using mouse model for evaluation of HIV vaccines6,245,891nusB polypeptides and polynucleotides and methods thereof6,245,542tRNA methyltransferase from Streptococcus pneumoniae6,238,900Polynucleotides encoding glutamyltrna synthetase from staphylococcus aureus6,238,887Ribosome recycling factor (FRR) of Staphylococcus aureus6,238,882GidA16,228,625metK from Streptococcus pneumoniae6,228,584DexB6,210,880Polymorphism analysis by nucleic acid structure probing with structure-bridgingoligonucleotides6,204,014DnaB6,197,549Ama6,197,300ftsZ6,194,170MurF of Streptococcus pneumoniae6,190,881Ribonucleotide diphosphate reductase, nrdF, of streptococcus pneumoniae6,168,797FabF6,165,992Histidine kinase6,165,991Sensor histidine kinase of Streptococcus pneumoniae6,165,764Polynucleotides encoding tRNA methyl transferases from Streptococcus pneumoniae6,162,619Sensor histidine kinase of streptococcus pneumoniae6,162,6186-phosphogluconate dehydrogenase of Streptococcus pneumoniae6,156,537Phospho-N-acetylmuramoyl-pentapeptide transferase of Streptococcus pneumoniae6,146,863Staphylococcus aureus 3-hydroxyacyl-CoA dehydrogenase6,146,846Primosome protein a of streptococcus pneumoniae6,140,079GidB6,140,061Response regulator6,111,074PyrH of Streptococcus pneumoniae6,110,723Yfii pseudouridine synthase6,110,685infB6,090,543Cleavage of nucleic acids6,060,294Alanyl tRNA synthetase from Staphylococcus aureus6,001,567Detection of nucleic acid sequences by invader-directed cleavage5,994,111Leucyl tRNA synthetase from staphylococcus aureus5,985,557Invasive cleavage of nucleic acids5,882,643Lep5,851,764Human prostate tumor inducing gene-1 and uses thereof5,843,669Cleavage of nucleic acid acid using thermostable methoanococcus jannaschii FEN-1endonucleases5,843,654Rapid detection of mutations in the p53 gene5,795,976Detection of nucleic acid heteroduplex molecules by denaturing high-performanceliquid chromatography and methods for comparative sequencing5,789,217DNA encoding asparaginyl tRNA synthetase from staphylococcus aureus5,786,197Lep5,776,750Alanyl tRNA synthetase polynucleoyides of staphylococcus5,763,246DNA encoding arginyl tRNA synthetase from staphylococcus aureus5,750,387DNA encoing leucyl TRNA synthetase from staphylococcus aureus5,688,646Mycoplasmas-agents for detecting and characterizing mycoplasmas in vitro (Seeabove)6,562,957Genomic sequence encoding endoglin and fragments thereof6,545,140DNA encoding an avian beta-defensin and uses thereof6,531,148Therapeutic agents6,495,661DNA encoding the outer membrane protein of Pasteurella multocida6,475,990Drugs, foods or drinks with the use of algae-derived physiologically active substances6,451,601Transiently immortalized cells for use in gene therapy6,403,564Ribavirin-interferon alfa combination therapy for eradicating detectable HCV-RNA inpatients having chronic hepatitis C infection6,399,373Nucleic acid encoding a retinoblastoma binding protein (RBP-7) and polymorphicmarkers associated with said nucleic acid6,368,600Parasitic helminth cuticlin nucleic acid molecules and uses thereof6,339,151Enzyme catalyzed therapeutic agents6,277,8305′-amino acid esters of ribavirin and the use of same to treat hepatitis C with interferon6,258,778Methods for accelerating bone and cartilage growth and repair6,248,329Parasitic helminth cuticlin nucleic acid molecules and uses thereof6,245,750Enzyme catalyzed therapeutic agents6,022,687Diagnosis of and therapy for hereditary haemorrhagic telangiectasia6,593,086Nucleic acid amplification methods6,583,266Nucleic acid and amino acid sequences relating to mycobacterium tuberculosis andleprae for diagnostics and therapeutics6,573,068Claudin-50 protein6,569,647Nucleic acid amplification method: ramification-extension amplification method(RAM)6,562,611FEN-1 endonucleases, mixtures and cleavage methods6,558,953Grapevine leafroll virus proteins and their uses6,558,909Haemobartonella PCR methods and materials6,558,905Diagnostics and therapeutics for osteoporosis6,558,902Infrared matrix-assisted laser desorption/ionization mass spectrometric analysis ofmacromolecules6,555,357FEN-1 endonuclease, mixtures and cleavage methods6,548,633Complementary DNA's encoding proteins with signal peptides6,531,648Grain processing method and transgenic plants useful therein6,524,795Diagnostics for cardiovascular disorders6,521,426Preparation of recombinant adenovirus carrying a rep gene of adeno-associated virus6,518,020Haemobartonella PCR methods and materials6,503,747Serotype-specific probes for Listeria monocytogenes6,495,325Detection and quantification of micro-organisms using amplification and restrictionenzyme analysis6,458,584Customized oligonucleotide microchips that convert multiple genetic information tosimple patterns, are portable and reusable6,458,535Detection of nucleic acids by multiple sequential invasive cleavages 026,444,876Acyl CoA: cholesterol acyltransferase related nucleic acid sequences6,436,399Nucleic acid encoding the major outer membrane protein of the causative agent ofhuman granulocytic ehrlichiosis and peptides encoded thereby6,432,649Methods for detecting Ehrlichia canis and Ehrlichia chaffeensis in vertebrate andinvertebrate hosts6,423,499PCR primers for detection and identification of plant pathogenic species, subspecies,and strains of acidovorax6,403,093Methods to detect granulocytic ehrlichiosis6,399,307Methods of quantifying viral load in an animal with a ribonuclease resistant RNApreparation6,387,617Catalytic nucleic acid and methods of use6,372,424Rapid detection and identification of pathogens6,348,314Invasive cleavage of nucleic acids6,329,138Method for detection of the antibiotic resistance spectrum of mycobacterium species6,312,922Complementary DNAs6,312,903Simulataneous detection, identification and differentiation of eubacterial taxa using ahybridization assay6,306,653Detection and treatment of breast disease6,300,091Herbicide target genes and methods6,300,072PCR methods and materials for detecting bartonella species6,287,779Detection of fermentation-related microorganisms6,268,142Diagnostics and therapeutics for diseases associated with an IL-1 inflammatoryhaplotype6,261,773Reagent for nucleic acid amplification and process for nucleic acid amplification6,252,130Production of somatic mosaicism in mammals using a recombinatorial substrate6,251,607PCR primers for the rapid and specific detection of Salmonella typhimurium6,248,519Detection of fermentation-related microorganisms6,221,582Polynucleic acid sequences for use in the detection and differentiation of prokaryoticorganisms6,214,982Ribonuclease resistant RNA preparation and utilization6,214,548Diagnostic methods for Cyclospora6,194,145Genus and species-specific identification of Legionella6,180,339Nucleic acid probes for the detection and identification of fungi6,103,468Rapid two-stage polymerase chain reaction method for detection of lactic acid bacteriain beer6,090,543Cleavage of nucleic acids6,033,858Detection of transmissible spongiform encephalopathies6,025,132Probes targeted to rRNA spacer regions, methods and kits for using said probes, forthe detection of respiratory tract pathogens6,001,567Detection of nucleic acid sequences by invader-directed cleavage6,001,564Species specific and universal DNA probes and amplification primers to rapidly detectand identify common bacterial pathogens and associated antibiotic resistance genesfrom clinical specimens for routine diagnosis in microbiology laboratories5,994,066Species-specific and universal DNA probes and amplification primers to rapidly detectand identify common bacterial pathogens and associated antibiotic resistance genesfrom clinical specimens for routine diagnosis in microbiology laboratories5,985,557Invasive cleavage of nucleic acids5,976,805Neisseria gonorrhoeae specific DNA fragment-GC35,958,693Extraction of DNA by boiling cells in an alkaline phenol/guanidine thiocyanatesolution5,948,888Neural thread protein gene expression and detection of Alzheimer's disease5,948,634Neural thread protein gene expression and detection of Alzheimer's disease5,942,391Nucleic acid amplification method: ramification-extension amplification method(RAM)5,939,262Ribonuclease resistant RNA preparation and utilization5,922,538Genetic markers and methods for the detection of Listeria monocytogenes and Listeriaspp5,919,625Ribonuclease resistant viral RNA standards5,912,117Method for diagnosis of lyme disease5,907,085Grapevine leafroll virus proteins and their uses5,876,924Nucleic acid amplification method hybridization signal amplification method (HSAM)5,843,669Cleavage of nucleic acid acid using thermostable methoanococcus jannaschii FEN-1endonucleases5,830,670Neural thread protein gene expression and detection of Alzheimer's disease5,795,976Detection of nucleic acid heteroduplex molecules by denaturing high-performanceliquid chromatography and methods for comparative sequencing5,763,169Nucleic acid probes for the detection and identification of fungi5,747,257Genetic markers and methods for the detection of escherichia coli serotype-0157:H75,744,306Methods for nucleic acid detection, sequencing, and cloning using exonuclease5,734,086Cytochrome P450.sub.lpr gene and its uses5,707,802Nucleic acid probes for the detection and identification of fungi5,693,467Mycoplasma 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